The objective of the proposed research is to elucidate the role of mechanical factors on the transport of proteins and other large molecules through the wall of the artery. This interdisciplinary project represents a coordinated program of theoretical and experimental investigations. The theoretical work involves the development of new models to clarify the mechanisms by which mechanical factors factors affect the behavior of the vesicles in the endothelial ceel and the diffusion of large molecules in the arterial wall. Parallel experimental studies will be performed to critically test the validity of the theories and to provide data for the improvement of the models. These experiments will be performed on isolated segments of dog carotid arteries subjected to rhythmic variations in artery length, pressure and flow, and the effects of these procedures on the transport of proteins and other large molecules will be determined by radioactivity assays and electron microscopic examinations. The results should improve our understanding of the mechanisms leading to atherosclerosis.